1. Description of the Core The Transgenic and Chimeric Mouse Facility is unique at the University of Pennsylvania, and provides pivotal services to generate genetically engineered mouse models and characterize them with relevance to digestive, liver and pancreatic research for this Center. In so doing, the NIH/NIDDK support for the Core permits the utilization of cost-effective technologies that would otherwise not be possible in individual labs, and fosters a unique environment for the promotion of interactions and scientific collaborations in this context. The Transgenic and Chimeric Mouse Facility was established in 1992 under the co-direction of Drs. Nancy Cooke and Stephen Liebhaber, and under the technical coordination of Dr. Jean Richa. The School of Medicine established the Core initially with financial support as well as equipment from the Cooke and Liebhaber laboratories, and with the charge from the Dean that its services be equitably available to the Medical Center's entire faculty. The entities that have contributed to the annual support of the Core include the NIDDK Digestive Diseases Research Core Center or at Penn referred to as the Center for Molecular Studies in Digestive and Liver Diseases (CMSDLD) since 1997, the NIDDK Diabetes and Endocrinology Research Center (DERC), the NCI Penn Abramson Cancer Center (ACC) and users' fees. For the CMSDLD, we will refer to Investigators or users as encompassing members and associate members, since a critical aspect of the CMSDLD and our Core to facilitate the growth of the associate members' labs, especially in pilot grants. The Core is located in a pathogen-free microbiologic barrier facility in the basement of the Clinical Research Building. The Core currently consists of a unified two-room microinjection laboratory (approximately 500 sq ft) and an adjacent mouse room with a capacity for 500-600 micro-isolator cages. These rooms are situated within a negative pressure suite (the 'barrier facility') provided with HEPA-filtered, class 100 air delivered through a vertical laminar flow system that changes the room air 15 to 20 times per hour. Temperature is controlled to +/-2F, and light/dark cycles are computer-controlled. The area is served by two pass-through autoclaves that sterilize all food, bedding, cages, and water used behind the barrier. Limited access to this facility is instrumental to insure animal health. All investigators must enter the facility via its double-door airlock and must wear protective outer clothing including gown, gloves, hair covering, mask and double shoe covers. The Core also has a newly constructed cryopreservation storage room in the adjacent John Morgan building that has been renovated and dedicated to the long-term storage of frozen embryo and Sperm.